EPA-0685 – Guanfacine XR (GXR) for Children and Adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD): Phase 3, Randomized, Double-Blind, Multicenter, Placebo- and Active-Reference Study

Abstract

Introduction:

GXR, a selective α2A-adrenergic agonist, is a non-stimulant treatment for ADHD (approved in the USA for children and adolescents and in Canada for children).

Objectives:

To assess the efficacy (symptoms and function) and safety of dose-optimized GXR compared with placebo in children and adolescents with ADHD.

Aims:

To evaluate the efficacy (symptom and function) and safety of GXR for the treatment of ADHD. An atomoxetine (ATX) arm was included to provide reference data against placebo (NCT01244490).

Methods:

Patients (6–17 years) were randomly assigned at baseline to dose-optimized GXR (6–12 years, 1–4 mg/day; 13–17 years, 1–7 mg/day), ATX (10–100mg/day) or placebo for 4 or 7 weeks. The primary efficacy measure is change from baseline in ADHD-Rating Scale-version IV (ADHD-RS-IV). Key secondary measures were defined as Clinical Global Impressions-Improvement (CGI-I) and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P). Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs.

Results:

Of 338 patients randomized, 272 (80.5%) completed the study. Placebo-adjusted differences in least squares (LS) mean in ADHD-RS-IV total score, percent improvement versus placebo for CGI-I, placebo-adjusted differences in LS mean change from baseline in WFIRS-P score (family and learning and school domains) are shown in the Table. The most common TEAEs for GXR were somnolence, headache, and fatigue; 8 (7%) TEAEs were severe.

Conclusions:

GXR was effective and well tolerated in children and adolescents with ADHD.

	GXR	ATX
Placebo-adjusted difference in LS mean change from baseline in ADHD-RS-IV total score (95% Cl, p-value; effect size)	−8.9 (−11.9, −5.8, p<0.001; 0.76)	−3.8 (−6.8, −0.7, p<0.05; 0.32)
Difference in improvement from placebo for CGI-I (95% Cl, p-value)	23.7% (11.1, 36.4; p<0.001)	12.1% (−0.9, 25.1; p<0.05)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; learning and school domain score (95%CI, p-value; effect size)	−0.22 (−0.36, −0.08, p<0.01; 0.42)	−0.16 (−0.31, −0.02, p<0.05; 0.32)
Placebo-adjusted difference in LS mean change from baseline in WFIRS-P; family domain score (95%CI, p-value; effect size)	−0.21 (−0.36, −0.06, p<0.01; 0.38)	−0.09 (−0.24, 0.06, p=0.242; 0.16)